One enantiomeric or diastereomeric isomer of a compound can possessed differing pharmacological activity than another. Pharmaceuticals compositions that contain compounds with multiple isomers increase the chances of undesired and adverse drug reactions. Regulatory agencies (e.g. FDA) throughout the world are currently reviewing the importance of diastereomeric and enantiomeric purity with regard to pharmaceutical and agrochemical products. New guidelines from such agencies have been key drivers for the focus on single isomeric products in these industries. Thus, there is a need to identify time and cost efficient methods of producing synthetically valuable compositions that result in single chiral compound compositions and methods for facilitating the separation and resolution chiral compounds.
Numerous chemical agents have been devised for the treatment of cancer with varying degrees of efficacy. However, no single drug has one hundred percent effectiveness against different cancers, and negative side-effects ranging from minor to serious are always present. On such compound that has received much attention due to its anticancer activity is camptothecin, a quinoline-based alkaloid found in the barks of the Chinese Camptotheca tree and the Asian nothapodytes tree. Camptothecin is also known by its chemical name 4(S)-ethyl-4-hydroxy-1H-pyrano-[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione.
It is well-known that camptothecin including and derivatives are useful in treating breast cancers, ovarian cancer, colon cancer, malignant melanoma, small cell lung cancer, thyroid cancers, lymphomas, leukemias, and more recently AIDS; however, drug delivery is complicated by the fact that camptothecin is water-insoluble in its unmodified state. Several derivatives of camptothecin have been developed in order to address these problems including glycosylated derivatives. Shull et al., U.S. Pat. No. 5,677,286, Shull et al., U.S. Pat. No. 5,932,709, and Bouscarel et al., U.S. Pat. No. 6,407,117 and references cited therein are all hereby incorporated by reference. Several of these glycosylated derivatives are undergoing clinical evaluation. The methods disclosed to prepare these glycosylated derivatives result in compositions that are comprised of a mixture of enantiomers and/or diastereomers. To this end, there is a need to identify methods of preparing these compositions that provide improved isomeric purities of these camptothecin derivatives.